Core B, the clinical core, is the patient care and clinical research component of the Program Project. It integrates into the program the resources of the MGH Addiction Services, including its drug abuse clinical research teach, its treatment facilities and the MGH Mallinckrodt General Clinical Research Center (GCRC). THIS Core manages human subject recruit, characterization and preparation, subjective clinical measurement and clinical safety. The specific aims are: (1) to recruit and characterize a sufficient sample of individuals' cocaine exposure, pattern and diagnostic status; (3) to prepare subjects so that they are able to comprehend, tolerate and comply with study procedures; (4) to obtain reliable and valid experimental subjective measures; and (5) to safely care for subjects following the imaging experiments by closely monitoring them in a medical unit, by counseling subjects to perceive the study experience as an educational process and by facilitating treatment engagement and safe discharge. Overall the past two years the Clinical Core has initiated its scientific pursuits, examining the following behaviorally and physiologically oriented questions. 1. What is the generalizability of these small study cohorts, particularly in terms of drug severity, motivation and long-term clinical outcomes? Are the non-treatment seekers in this study distinct from treatment seekers, particularly in terms of motivation? Do these infusion studies in any way contribute to beneficial or adverse long-term clinical outcomes? 2. Laboratory markers may aid self-report reliability of drug use. Are hair analyses or other measures of substance use valuable means to improve our subject characterization by validating other clinical assessments? 3. Clinical correlates of physiologic response: Is there any correlation between the physiologic variables measured during in vivo acute cocaine administration and subjects' recent or past clinical history of cocaine dependence? 4. Neuroendocrine system response: Given studies suggesting that HPA axis response may influence both cocaine reinforcement and symptoms that are clinically similar to cocaine withdrawal, to what extent are these systems involved in the phenomenology of cocaine use and/or withdrawal. Currently, these sub-studies have employed relatively small cohorts, compared to the samples in human clinical studies that typically are necessary to answer questions such as those above. To adequately explore each question, additional subjects are required for adequate comparisons. The new paradigms proposed in the human experimental project are expected to yield differential behavioral and possibly neuroendocrine responses that will help elucidate questions about subjective euphoria, craving and expectancy. The Clinical Core will continue to serve its previous clinical management role, will increase its efforts to recruit and track the larger subject pool needed for the proposed Project I work and will add these scientific sub-studies that are relevant to its primary mission.